Item type |
デフォルトアイテムタイプ(フル)(1) |
公開日 |
2020-05-22 |
タイトル |
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タイトル |
Targeting Excessive EZH1 and EZH2 Activities for Abnormal Histone Methylation and Transcription Network in Malignant Lymphomas |
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言語 |
en |
作成者 |
Yamagishi, Makoto
Hori, Makoto
Fujikawa, Dai
Ohsugi, Takeo
Honma, Daisuke
Adachi, Nobuaki
Katano, Harutaka
Hishima, Tsunekazu
Kobayashi, Seiichiro
Nakano, Kazumi
Nakashima, Makoto
Iwanaga, Masako
Utsunomiya, Atae
Tanaka, Yuetsu
Okada, Seiji
Tsukasaki, Kunihiro
Tobinai, Kensei
Araki, Kazushi
Watanabe, Toshiki
Uchimaru, Kaoru
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アクセス権 |
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アクセス権 |
open access |
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アクセス権URI |
http://purl.org/coar/access_right/c_abf2 |
権利情報 |
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言語 |
en |
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権利情報 |
Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 |
権利情報 |
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言語 |
en |
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権利情報Resource |
https://creativecommons.org/licenses/by-nc-nd/4.0/ |
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権利情報 |
https://creativecommons.org/licenses/by-nc-nd/4.0/ |
内容記述 |
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内容記述タイプ |
Other |
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内容記述 |
Although global H3K27me3 reprogramming is a hallmark of cancer, no effective therapeutic strategy for H3K27me3-high malignancies harboring EZH2(WT/WT) has yet been established. We explore epigenome and transcriptome in EZH2(WT/WT) and EZH2(WT/Mu) aggressive lymphomas and show that mutual interference and compensatory function of co-expressed EZH1 and EZH2 rearrange their own genome-wide distribution, thereby establishing restricted chromatin and gene expression signatures. Direct comparison of leading compounds introduces potency and a mechanism of action of the EZH1/2 dual inhibitor (valemetostat). The synthetic lethality is observed in all lymphoma models and primary adult T cell leukemia-lymphoma (ATL) cells. Opposing actions of EZH1/2-polycomb and SWI/SNF complexes are required for facultative heterochromatin formation. Inactivation of chromatin-associated genes (ARID1A, SMARCA4/BRG1, SMARCB1/SNF5, KDM6A/UTX, BAP1, KMT2D/MLL2) and oncovirus infection (HTLV-1, EBV) trigger EZH1/2 perturbation and H3K27me3 deposition. Our study provides the mechanism-based rationale for chemical dual targeting of EZH1/2 in cancer epigenome. |
内容記述 |
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内容記述タイプ |
Other |
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内容記述 |
論文 |
出版者 |
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言語 |
en |
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出版者 |
Cell Press |
言語 |
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言語 |
eng |
資源タイプ |
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資源タイプ |
journal article |
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資源タイプ識別子 |
http://purl.org/coar/resource_type/c_6501 |
出版タイプ |
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出版タイプ |
VoR |
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出版タイプResource |
http://purl.org/coar/version/c_970fb48d4fbd8a85 |
識別子 |
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識別子 |
http://hdl.handle.net/20.500.12000/45873 |
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識別子タイプ |
HDL |
関連情報 |
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識別子タイプ |
DOI |
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関連識別子 |
https://doi.org/10.1016/j.celrep.2019.10.083 |
関連情報 |
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識別子タイプ |
DOI |
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関連識別子 |
https://doi.org/10.1016/j.celrep.2019.10.083 |
収録物識別子 |
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収録物識別子タイプ |
ISSN |
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収録物識別子 |
2211-1247 |
収録物名 |
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言語 |
en |
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収録物名 |
Cell reports |
書誌情報 |
巻 29,
号 8,
p. 2321-2337,
発行日 2019-11-19
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